Sodium hydride → N-BOC-N-(3-chloro-4-iodophenyl)alanine iso-butyl ester

HRID 1739196Notes

Reaction equation

HRID 1739196 reaction equation
ClC1C=C(C=CC=1I)N.[C:10]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:24])=[C:20]([Cl:25])[CH:19]=1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[H-].[Na+].Br[CH:29]([CH3:37])[C:30]([O:32][CH2:33][CH:34]([CH3:36])[CH3:35])=[O:31]>CN(C=O)C.ClCCl>[CH2:33]([O:32][C:30](=[O:31])[C@H:29]([CH3:37])[N:17]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:18]1[CH:23]=[CH:22][C:21]([I:24])=[C:20]([Cl:25])[CH:19]=1)[CH:34]([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 2829263-Chloro-4-iodoanilineHCID 522337Isobutyl 2-bromopropionateHCID 22592440tert-Butyl (3-chloro-4-iodophenyl)carbamate2×

Product 1

HCID 21341411N-BOC-N-(3-chloro-4-iodophenyl)alanine iso-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Following General Procedure R above and using 3-chloro-4-iodoaniline (Aldrich), N-BOC-3-chloro-4-iodoaniline was prepared. To a stirred slurry of 5.0 equivalents of sodium hydride in DMF was added 1.0 equivalent of N-BOC-3-chloro-4-iodoaniline and then 1.1 equivalents of iso-butyl 2-bromopropionate (from Example D above) were slowly added. The reaction was heated to 100° C. for 10 hours, cooled, diluted with dichloromethane and washed with cold 1N HCl, water and brine. The solvents were removed at reduced pressure and the residue was chromatographed to provide N-BOC-N-(3-chloro-4-iodophenyl)alanine iso-butyl ester as a clear oil. Following General Procedure N above, the BOC group was removed from N-BOC-N-(3-chloro-4-iodophenyl)alanine iso-butyl ester to provide the title compound. The BOC-removal reaction was monitored by tlc on silica gel (Rf=0.58 in 30% EtOAc/hexanes) and purification was by preparative plate chromatography (silica gel using 30% EtOAc/hexanes as the eluant). The compound was further purified by chromatography on an HPLC chiral column (Chiralcel OD).

Workup

  1. customwas prepared
  2. temperaturecooled
  3. washwashed with cold 1N HCl, water and brine
  4. customThe solvents were removed at reduced pressure
  5. customthe residue was chromatographed

Sources & evidence

ORD record
ord-8b5e7b3b2cbc468aa96a6f04f496d0bc
Source dataset
uspto-grants-1999_10
Patent number
US05965614

Reaction notes

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